TITLE:
Leishmania donovani-Induced Immune Dysregulation among Sudanese Patients with Visceral and Post Kala-Azar Dermal Leishmaniases: Possible Roles in Pathogenesis
AUTHORS:
Elsamani Elmotwafig Mohamed Elsammani, Brima Younis Musa, Mona Elfaki Eltahir Elfaki, Ahmed Mudawi Mudawi, Eltahir Awad Gasim Khalil
KEYWORDS:
L. donovani-Induced Immune Suppression, Tissue-Based Autoimmunity, Pathogenesis
JOURNAL NAME:
Advances in Infectious Diseases,
Vol.10 No.5,
November
25,
2020
ABSTRACT: L. donovani infections (visceral and post kala-azar dermal leishmaniases) are characterized by infection-induced reversible immune suppression. Autoimmunity is a well-documented phenomenon among patients with primary immune deficiencies. This study aimed to study auto-immune phenomena accompanying L. donovani infections. In a prospective case-controlled study and following informed consent, 155 individuals with visceral leishmaniasis (VL; n = 62), post kala-azar dermal leishmaniasis (PKDL; n = 31) and apparently healthy volunteers (n = 62) were recruited. Sera antinuclear (ANA), anti-dsDNA, anti-thyroid peroxidase (TPO), anti-smooth muscles (ASMA) and F-actin auto-antibodies were measured using ELISA and indirect immune-fluorescence assay. The mean ages of VL, PDKL patients and apparently healthy volunteers were: 17.5 ± 12.5, 15.0 ± 7.0 and 17.5 ± 9.5 years with Male:Female ratios of 2:0, 1:2 and 1:5 respectively. Significantly high frequencies of F-actin (74.2%; 46/62) and ASMA (50%; 31/62) auto-antibodies were seen among VL patients (p = 0.003, p = 0.001) compared to apparently healthy volunteers. Likewise, significantly high frequencies of F-actin (64.5%; 20/31; p = 0.001), ASMA (42%; 13/31; p = 0.003), ANA (36%; 11/31; p = 0.001) and anti-dsDNA (16%; 5/31; p = 0.01) auto-antibodies were seen among PKDL patients. Development of tissue-based autoantibodies in L. donovani infections probably indicates loss of peripheral tolerance with activation of circulating auto-reactive T and B cells probably contributing to disease pathogenesis (increased bilirubin/liver enzymes, prolonged QT interval/arrythmias and blood cytopenias). In conclusion, L. donovani infection-induced immune suppression with development of tissue-based auto-antibodies is prevalent among Sudanese patients with VL and PKDL leishmaniases and contributes to some aspects of the disease pathogenesis.